Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis c-IAP2 is under NF-κB control

Members of the NF-κB/Rel and inhibitor of apoptosis (IAP) protein families have been implicated in signal transduction programs that prevent cell death elicited by the cytokine tumor necrosis factor α (TNF). Although NF-κB appears to stimulate the expression of specific protective genes, neither the identities of these genes nor the precise role of IAP proteins in this anti-apoptotic process are known. We demonstrate here that NF-κB is required for TNF-mediated induction of the gene encoding human c-IAP2. When overexpressed in mammalian cells, c-IAP2 activates NF-κB and suppresses TNF cytotoxicity. Both of these c-IAP2 activities are blocked in vivo by coexpressing a dominant form of IκB that is resistant to TNF-induced degradation. In contrast to wild-type c-IAP2, a mutant lacking the C-terminal RING domain inhibits NF-κB induction by TNF and enhances TNF killing. These findings suggest that c-IAP2 is critically involved in TNF signaling and exerts positive feedback control on NF-κB via an IκB targeting mechanism. Functional coupling of NF-κB and c-IAP2 during the TNF response may provide a signal amplification loop that promotes cell survival rather than death.

The mechanical properties of Saccharomyces cerevisiae

Cell-wall mechanical properties play an integral part in the growth and form of Saccharomyces cerevisiae. In contrast to the tremendous knowledge on the genetics of S. cerevisiae, almost nothing is known about its mechanical properties. We have developed a micromanipulation technique to measure the force required to burst single cells and have recently established a mathematical model to extract the mechanical properties of the cell wall from such data. Here we determine the average surface modulus of the S. cerevisiae cell wall to be 11.1 ± 0.6 N/m and 12.9 ± 0.7 N/m in exponential and stationary phases, respectively, giving corresponding Young's moduli of 112 ± 6 MPa and 107 ± 6 MPa. This result demonstrates that yeast cell populations strengthen as they enter stationary phase by increasing wall thickness and hence the surface modulus, without altering the average elastic properties of the cell-wall material. We also determined the average breaking strain of the cell wall to be 82% ± 3% in exponential phase and 80% ± 3% in stationary phase. This finding provides a failure criterion that can be used to predict when applied stresses (e.g., because of fluid flow) will lead to wall rupture. This work analyzes yeast compression experiments in different growth phases by using engineering methodology.

Targeted inactivation of sister of P-glycoprotein gene (spgp) in mice results in nonprogressive but persistent intrahepatic cholestasis

Mutations in the sister of P-glycoprotein (Spgp) or bile salt export pump (BSEP) are associated with Progressive Familial Intrahepatic Cholestasis (PFIC2). Spgp is predominantly expressed in the canalicular membranes of liver. Consistent with in vitro evidence demonstrating the involvement of Spgp in bile salt transport, PFIC2 patients secrete less than 1% of biliary bile salts compared with normal infants. The disease rapidly progresses to hepatic failure requiring liver transplantation before adolescence. In this study, we show that the knockout of spgp gene in mice results in intrahepatic cholestasis, but with significantly less severity than PFIC2 in humans. Some unexpected characteristics are observed. Notably, although the secretion of cholic acid in mutant mice is greatly reduced (6% of wild-type), total bile salt output in mutant mice is about 30% of wild-type. Also, secretion of an unexpectedly large amount of tetra-hydroxylated bile acids (not detected in wild-type) is observed. These results suggest that hydroxylation and an alternative canalicular transport mechanism for bile acids compensate for the absence of Spgp function and protect the mutant mice from severe cholestatic damage. In addition, the spgp−/− mice display a significant increase in the secretion of cholesterol and phospholipids into the bile. This latter observation in spgp−/− mice suggests that intrahepatic, rather than intracanalicular, bile salts are the major driving force for the biliary lipid secretion. The spgp−/− mice thus provide a unique model for gaining new insights into therapeutic intervention for intrahepatic cholestasis and understanding mechanisms associated with lipid homeostasis.

A novel microbial habitat in the mid-ocean ridge subseafloor

The subseafloor at the mid-ocean ridge is predicted to be an excellent microbial habitat, because there is abundant space, fluid flow, and geochemical energy in the porous, hydrothermally influenced oceanic crust. These characteristics also make it a good analog for potential subsurface extraterrestrial habitats. Subseafloor environments created by the mixing of hot hydrothermal fluids and seawater are predicted to be particularly energy-rich, and hyperthermophilic microorganisms that broadly reflect such predictions are ejected from these systems in low-temperature (≈15°C), basalt-hosted diffuse effluents. Seven hyperthermophilic heterotrophs isolated from low-temperature diffuse fluids exiting the basaltic crust in and near two hydrothermal vent fields on the Endeavour Segment, Juan de Fuca Ridge, were compared phylogenetically and physiologically to six similarly enriched hyperthermophiles from samples associated with seafloor metal sulfide structures. The 13 organisms fell into four distinct groups: one group of two organisms corresponding to the genus Pyrococcus and three groups corresponding to the genus Thermococcus. Of these three groups, one was composed solely of sulfide-derived organisms, and the other two related groups were composed of subseafloor organisms. There was no evidence of restricted exchange of organisms between sulfide and subseafloor habitats, and therefore this phylogenetic distinction indicates a selective force operating between the two habitats. Hypotheses regarding the habitat differences were generated through comparison of the physiology of the two groups of hyperthermophiles; some potential differences between these habitats include fluid flow stability, metal ion concentrations, and sources of complex organic matter.

Using three-dimensional microfluidic networks for solving computationally hard problems

This paper describes the design of a parallel algorithm that uses moving fluids in a three-dimensional microfluidic system to solve a nondeterministically polynomial complete problem (the maximal clique problem) in polynomial time. This algorithm relies on (i) parallel fabrication of the microfluidic system, (ii) parallel searching of all potential solutions by using fluid flow, and (iii) parallel optical readout of all solutions. This algorithm was implemented to solve the maximal clique problem for a simple graph with six vertices. The successful implementation of this algorithm to compute solutions for small-size graphs with fluids in microchannels is not useful, per se, but does suggest broader application for microfluidics in computation and control.

Illite and hydrocarbon exploration

Illite is a general term for the dioctahedral mica-like clay mineral common in sedimentary rocks, especially shales. Illite is of interest to the petroleum industry because it can provide a K-Ar isotope date that constrains the timing of basin heating events. It is critical to establish that hydrocarbon formation and migration occurred after the formation of the trap (anticline, etc.) that is to hold the oil. Illite also may precipitate in the pores of sandstone reservoirs, impeding fluid flow. Illite in shales is a mixture of detrital mica and its weathering products with diagenetic illite formed by reaction with pore fluids during burial. K-Ar ages are apparent ages of mixtures of detrital and diagenetic end members, and what we need are the ages of the end members themselves. This paper describes a methodology, based on mineralogy and crystallography, for interpreting the K-Ar ages from illites in sedimentary rocks and for estimating the ages of the end members.

Protonation dynamics of the extracellular and cytoplasmic surface of bacteriorhodopsin in the purple membrane.

The dynamics of proton binding to the extracellular and the cytoplasmic surfaces of the purple membrane were measured by laser-induced proton pulses. Purple membranes, selectively labeled by fluorescein at Lys-129 of bacteriorhodopsin, were pulsed by protons released in the aqueous bulk from excited pyranine (8-hydroxy-1,3,6-pyrenetrisulfonate) and the reaction of protons with the indicators was measured. Kinetic analysis of the data imply that the two faces of the membrane differ in their buffer capacities and in their rates of interaction with bulk protons. The extracellular surface of the purple membrane contains one anionic proton binding site per protein molecule with pK = 5.1. This site is within a Coulomb cage radius (approximately 15 A) from Lys-129. The cytoplasmic surface of the purple membrane bears 4-5 protonable moieties (pK = 5.1) that, due to close proximity, function as a common proton binding site. The reaction of the proton with this cluster is at a very fast rate (3.10(10) M-1.s-1). The proximity between the elements is sufficiently high that even in 100 mM NaCl they still function as a cluster. Extraction of the chromophore retinal from the protein has a marked effect on the carboxylates of the cytoplasmic surface, and two to three of them assume positions that almost bar their reaction with bulk protons. The protonation dynamics determined at the surface of the purple membrane is of relevance both for the vectorial proton transport mechanism of bacteriorhodopsin and for energy coupling, not only in halobacteria, but also in complex chemiosmotic systems such as mitochondrial and thylakoid membranes.

What electrical measurements can say about changes in fault systems.

Earthquake zones in the upper crust are usually more conductive than the surrounding rocks, and electrical geophysical measurements can be used to map these zones. Magnetotelluric (MT) measurements across fault zones that are parallel to the coast and not too far away can also give some important information about the lower crustal zone. This is because the long-period electric currents coming from the ocean gradually leak into the mantle, but the lower crust is usually very resistive and very little leakage takes place. If a lower crustal zone is less resistive it will be a leakage zone, and this can be seen because the MT phase will change as the ocean currents leave the upper crust. The San Andreas Fault is parallel to the ocean boundary and close enough to have a lot of extra ocean currents crossing the zone. The Loma Prieta zone, after the earthquake, showed a lot of ocean electric current leakage, suggesting that the lower crust under the fault zone was much more conductive than normal. It is hard to believe that water, which is responsible for the conductivity, had time to get into the lower crustal zone, so it was probably always there, but not well connected. If this is true, then the poorly connected water would be at a pressure close to the rock pressure, and it may play a role in modifying the fluid pressure in the upper crust fault zone. We also have telluric measurements across the San Andreas Fault near Palmdale from 1979 to 1990, and beginning in 1985 we saw changes in the telluric signals on the fault zone and east of the fault zone compared with the signals west of the fault zone. These measurements were probably seeing a better connection of the lower crust fluids taking place, and this may result in a fluid flow from the lower crust to the upper crust. This could be a factor in changing the strength of the upper crust fault zone.

Electrical investigation of p-type 4H-SiC heavily doped by ion implantation

In the last decades, an increasing interest in the research field of wide bandgap semiconductors was observed, mostly due to the progressive approaching of silicon-based devices to their theoretical limits. 4H-SiC is an example among these, and is a mature compound for applications. The main advantages offered 4H-SiC in comparison with silicon are an higher breakdown field, an higher thermal conductivity, a higher operating temperature, very high hardness and melting point, biocompatibility, but also low switching losses in high frequencies applications and lower on-resistances in unipolar devices. Then, 4H-SiC power devices offer great performance improvement; moreover, they can work in hostile environments where silicon power devices cannot function. Ion implantation technology is a key process in the fabrication of almost all kinds of SiC devices, owing to the advantage of a spatially selective doping. This work is dedicated to the electrical investigation of several differently-processed 4H-SiC ion- implanted samples, mainly through Hall effect and space charge spectroscopy experiments. It was also developed the automatic control (Labview) of several experiments. In the work, the effectiveness of high temperature post-implant thermal treatments (up to 2000°C) were studied and compared considering: (i) different methods, (ii) different temperatures and (iii) different duration of the annealing process. Preliminary p + /n and Schottky junctions were also investigated as simple test devices. 1) Heavy doping by ion implantation of single off-axis 4H-SiC layers The electrical investigation is one of the most important characterization of ion-implanted samples, which must be submitted to mandatory post-implant thermal treatment in order to both (i) recover the lattice after ion bombardment, and (ii) address the implanted impurities into lattice sites so that they can effectively act as dopants. Electrical investigation can give fundamental information on the efficiency of the electrical impurity activation. To understand the results of the research it should be noted that: (a) To realize good ohmic contacts it is necessary to obtain spatially defined highly doped regions, which must have conductivity as low as possible. (b) It has been shown that the electrical activation efficiency and the electrical conductivity increase with the annealing temperature increasing. (c) To maximize the layer conductivity, temperatures around 1700°C are generally used and implantation density high till to 10 21 cm -3 . In this work, an original approach, different from (c), is explored by the using very high annealing temperature, around 2000°C, on samples of Al + -implant concentration of the order of 10 20 cm -3 . Several Al + -implanted 4H-SiC samples, resulting of p-type conductivity, were investigated, with a nominal density varying in the range of about 1-5∙10 20 cm -3 and subjected to two different high temperature thermal treatments. One annealing method uses a radiofrequency heated furnace till to 1950°C (Conventional Annealing, CA), the other exploits a microwave field, providing a fast heating rate up to 2000°C (Micro-Wave Annealing, MWA). In this contest, mainly ion implanted p-type samples were investigated, both off-axis and on-axis <0001> semi-insulating 4H-SiC. Concerning p-type off-axis samples, a high electrical activation of implanted Al (50-70%) and a compensation ratio below 10% were estimated. In the work, the main sample processing parameters have been varied, as the implant temperature, CA annealing duration, and heating/cooling rates, and the best values assessed. MWA method leads to higher hole density and lower mobility than CA in equivalent ion implanted layers, resulting in lower resistivity, probably related to the 50°C higher annealing temperature. An optimal duration of the CA treatment was estimated in about 12-13 minutes. A RT resistivity on the lowest reported in literature for this kind of samples, has been obtained. 2) Low resistivity data: variable range hopping Notwithstanding the heavy p-type doping levels, the carrier density remained less than the critical one required for a semiconductor to metal transition. However, the high carrier densities obtained was enough to trigger a low temperature impurity band (IB) conduction. In the heaviest doped samples, such a conduction mechanism persists till to RT, without significantly prejudice the mobility values. This feature can have an interesting technological fall, because it guarantee a nearly temperature- independent carrier density, it being not affected by freeze-out effects. The usual transport mechanism occurring in the IB conduction is the nearest neighbor hopping: such a regime is effectively consistent with the resistivity temperature behavior of the lowest doped samples. In the heavier doped samples, however, a trend of the resistivity data compatible with a variable range hopping (VRH) conduction has been pointed out, here highlighted for the first time in p-type 4H-SiC. Even more: in the heaviest doped samples, and in particular, in those annealed by MWA, the temperature dependence of the resistivity data is consistent with a reduced dimensionality (2D) of the VRH conduction. In these samples, TEM investigation pointed out faulted dislocation loops in the basal plane, whose average spacing along the c-axis is comparable with the optimal length of the hops in the VRH transport. This result suggested the assignment of such a peculiar behavior to a kind of spatial confinement into a plane of the carrier hops. 3) Test device the p + -n junction In the last part of the work, the electrical properties of 4H-SiC diodes were also studied. In this case, a heavy Al + ion implantation was realized on n-type epilayers, according to the technological process applied for final devices. Good rectification properties was shown from these preliminary devices in their current-voltage characteristics. Admittance spectroscopy and deep level transient spectroscopy measurements showed the presence of electrically active defects other than the dopants ones, induced in the active region of the diodes by ion implantation. A critical comparison with the literature of these defects was performed. Preliminary to such an investigation, it was assessed the experimental set up for the admittance spectroscopy and current-voltage investigation and the automatic control of these measurements.

Difference schemes for numerical solutions of lagging models of heat conduction

Non-Fourier models of heat conduction are increasingly being considered in the modeling of microscale heat transfer in engineering and biomedical heat transfer problems. The dual-phase-lagging model, incorporating time lags in the heat flux and the temperature gradient, and some of its particular cases and approximations, result in heat conduction modeling equations in the form of delayed or hyperbolic partial differential equations. In this work, the application of difference schemes for the numerical solution of lagging models of heat conduction is considered. Numerical schemes for some DPL approximations are developed, characterizing their properties of convergence and stability. Examples of numerical computations are included.

An approach to the application of shift-and-add algorithms on engineering and industrial processes

Different kinds of algorithms can be chosen so as to compute elementary functions. Among all of them, it is worthwhile mentioning the shift-and-add algorithms due to the fact that they have been specifically designed to be very simple and to save computer resources. In fact, almost the only operations usually involved with these methods are additions and shifts, which can be easily and efficiently performed by a digital processor. Shift-and-add algorithms allow fairly good precision with low cost iterations. The most famous algorithm belonging to this type is CORDIC. CORDIC has the capability of approximating a wide variety of functions with only the help of a slight change in their iterations. In this paper, we will analyze the requirements of some engineering and industrial problems in terms of type of operands and functions to approximate. Then, we will propose the application of shift-and-add algorithms based on CORDIC to these problems. We will make a comparison between the different methods applied in terms of the precision of the results and the number of iterations required.

Numerical resolution of Emden's equation using Adomian polynomials

Purpose: In this paper the authors aim to show the advantages of using the decomposition method introduced by Adomian to solve Emden's equation, a classical non‐linear equation that appears in the study of the thermal behaviour of a spherical cloud and of the gravitational potential of a polytropic fluid at hydrostatic equilibrium. Design/methodology/approach: In their work, the authors first review Emden's equation and its possible solutions using the Frobenius and power series methods; then, Adomian polynomials are introduced. Afterwards, Emden's equation is solved using Adomian's decomposition method and, finally, they conclude with a comparison of the solution given by Adomian's method with the solution obtained by the other methods, for certain cases where the exact solution is known. Findings: Solving Emden's equation for n in the interval [0, 5] is very interesting for several scientific applications, such as astronomy. However, the exact solution is known only for n=0, n=1 and n=5. The experiments show that Adomian's method achieves an approximate solution which overlaps with the exact solution when n=0, and that coincides with the Taylor expansion of the exact solutions for n=1 and n=5. As a result, the authors obtained quite satisfactory results from their proposal. Originality/value: The main classical methods for obtaining approximate solutions of Emden's equation have serious computational drawbacks. The authors make a new, efficient numerical implementation for solving this equation, constructing iteratively the Adomian polynomials, which leads to a solution of Emden's equation that extends the range of variation of parameter n compared to the solutions given by both the Frobenius and the power series methods.

Thermal model for charring rate calculation in wooden cellular slabs under fire

Wood is a natural and traditional building material, as popular today as ever, and presents advantages. Physically, wood is strong and stiff, but compared with other materials like steel is light and flexible. Wood material can absorb sound very effectively and it is a relatively good heat insulator. But dry wood burns quite easily and produces a great deal of heat energy. The main disadvantage is the high level of combustion when exposed to fire, where the point at which it catches fire is from 200–400°C. After fire exposure, is need to determine if the charred wooden structures are safe for future use. Design methods require the use of computer modelling to predict the fire exposure and the capacity of structures to resist those action. Also, large or small scale experimental tests are necessary to calibrate and verify the numerical models. The thermal model is essential for wood structures exposed to fire, because predicts the charring rate as a function of fire exposure. The charring rate calculation of most structural wood elements allows simple calculations, but is more complicated for situations where the fire exposure is non-standard and in wood elements protected with other materials. In this work, the authors present different case studies using numerical models, that will help professionals analysing woods elements and the type of information needed to decide whether the charred structures are adequate or not to use. Different thermal models representing wooden cellular slabs, used in building construction for ceiling or flooring compartments, will be analysed and submitted to different fire scenarios (with the standard fire curve exposure). The same numerical models, considering insulation material inside the wooden cellular slabs, will be tested to compare and determine the fire time resistance and the charring rate calculation.

(Table T1) Physical properties of minicores from ODP Leg 193 sites, PACMANUS field

Permeability of the ocean crust is one of the most crucial parameters for constraining submarine fluid flow systems. Active hydrothermal fields are dynamic areas where fluid flow strongly affects the geochemistry and biology of the surrounding environment. There have been few permeability measurements in these regions, especially in felsic-hosted hydrothermal systems. We present a data set of 38 permeability and porosity measurements from the PACMANUS hydrothermal field, an actively venting, felsic hydrothermal field in the eastern Manus Basin. Permeability was measured using a complex transient method on 2.54-cm minicores. Permeability varies greatly between the samples, spanning over five orders of magnitude. Permeability decreases with both depth and decreasing porosity. When the alteration intensity of individual samples is considered, relationships between depth and porosity and permeability become more clearly defined. For incompletely altered samples (defined as >5% fresh rock), permeability and porosity are constant with depth. For completely altered samples (defined as <5% fresh rock), permeability and porosity decrease with depth. On average, the permeability values from the PACMANUS hydrothermal field are greater than those in other submarine environments using similar core-scale laboratory measurements; the average permeability, 4.5 x 10-16 m**2, is two to four orders of magnitude greater than in other areas. Although the core-scale permeability is higher than in other seafloor environments, it is still too low to obtain the fluid velocities observed in the PACMANUS hydrothermal field based on simplified analytical calculations. It is likely that core-scale permeability measurements are not representative of bulk rock permeability of the hydrothermal system overall, and that the latter is predominantly fracture controlled.